Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex: in vivo microdialysis study.
OBJECTIVE
In order to elucidate the relevance between the delayed onset of clinical efficacy of selective serotonin re-uptake inhibitors (SSRI) and extracellular 5-HT levels in the medial prefrontal cortex, the present study compared the ability of low-dose (3 mg/kg) and high-dose (30 mg/kg) citalopram to increase extracellular 5-HT levels in the medial prefrontal cortex following repeated citalopram treatment using in vivo microdialysis.


METHODS
An SSRI, citalopram, was given 10 mg/kg, s.c. twice daily for 6 days and once on the seventh day in rats. On the eighth day, rats received a single injection of citalopram (3 or 30 mg/kg s.c.), and extracellular 5-HT levels were assessed in the medial prefrontal cortex of rats using in vivo brain microdialysis.


RESULTS
There was no significant difference in basal extracellular 5-HT levels between the repeated citalopram group and the repeated saline group. The low-challenge dose of citalopram (3 mg/kg) produced significantly greater increases (170-200% at each time point) in the repeated citalopram group than in the repeated saline group (150%). The high-challenge dose of citalopram (30 mg/kg), however, increased extracellular 5-HT levels by 200-250% of basal levels in the repeated citalopram group, which was similar to the increases in the repeated saline group.


CONCLUSIONS
Repeated SSRI treatment enhances the effect of low-dose SSRI on extracellular 5-HT levels but not that of high-dose SSRI.
Muraki
Ihoko
I
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Inoue
Takeshi
T
Hashimoto
Shinji
S
Izumi
Takeshi
T
Koyama
Tsukasa
T
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors